The overall objective for this project is to identify the nature of the prolonged and severe T-Lymphocyte deficiency observed in many recipients of unrelated marrow grafts. Unrelated marrow transplantation is associated with a significant increase in acute and chronic Graft Versus host Disease (GVHD), which can be dramatically reduced when mature T cells are removed from the marrow prior to transplantation. T cell depleted marrow transplantation is, however, associated with an increased frequency of Graft Rejection (GR) and Graft Failure (GF), which in most instances is caused by host derived T lymphocytes. But even in absence of severe GVHD or GR/GF, unrelated marrow transplantation is associated with severe, prolonged immunodeficiency and adult patients are particularly susceptible to this life-threatening complication. The objective for this project is to determine if characteristic patterns of T lymphocyte responsiveness in vitro can be identified for marrow transplant recipients post transplantation. Representative patients will be selected for detailed analysis based on clinical and laboratory data in order to identify patterns of T lymphocyte responsiveness, characteristic for patient age, degree of HLA matching and unmodified vs T cell depleted marrow. The studies are designed for the purpose of identifying abnormalities in TCR mediated T lymphocyte subset function. The project is designed with the following specific aims: (1) To determine TCR mediated in vitro responses of TCR alpha/beta CD4+ T cells with particular emphasis on the CD45RA+ and CD45RO+ subsets in patients post-transplantation. The studies will attempt to identify the immunological basis for prolonged T lymphocyte hyporesponsiveness observed in some patients. (2) To determine TCR mediated in vitro responses of TCR alpha/beta+ and laudelta+ CD8+ T cells in patients post-transplantation, and identify patterns characteristic for patients with prolonged T lymphocyte deficiency post-transplantation.